Dual Role of 5-Lipoxygenase in Osteoclastogenesis in Bacterial-induced Apical Periodontitis

Paula-Silva, Francisco Wanderley Garcia; Petean, Igor Bassi Ferreira; Silva, Léa Assed Bezerra da; Faccioli, Lúcia Helena

doi:10.1016/j.joen.2015.12.003

Cited by 30 publications

(29 citation statements)

References 39 publications

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“…Ltda., Barueri, SP, Brazil), root canals were located with a #06 K-file (Les Fils d’ Auguste Maillefer S/A, Ballaigues, Switzerland), and the radicular pulp tissue was removed. 18 Then, 10 µL of LPS suspension (1.0 mg/mL) from E. coli 0127: B8 (L3129; Sigma-Aldrich Corp., St. Louis, MO, USA) were inoculated within root canals of each tooth by means of an automatic micropipette. The teeth were sealed with conventional glass ionomer cement (S.S. White Dental Articles Ltda, Rio de Janeiro, RJ, Brazil), mixed in accordance with the manufacturer's instructions.…”

Section: Methodsmentioning

confidence: 99%

“…Interestingly, in vitro , a COX-2 selective inhibitor (celecoxib) impaired osteoclast formation, suggesting prostaglandins have a role in bone resorption. 11 , 17 We have previously demonstrated that the 5-lipoxygenase inhibitor is able to regulate RANK/RANKL/OPG in apical periodontitis; 18 however, studies showing the effects of a COX-2 selective inhibitor and a non-selective COX-2 inhibitor on the regulation of RANK, RANKL, OPG and other genes involved in bone metabolism following root canal inoculation with LPS has not been reported. Because infection, inflammation and bone resorption are closely related events in apical periodontitis development, we hypothesized that blockage in the cyclooxygenase pathway would change the signaling involved in periapical bone response to bacterial lipopolysaccharide.…”

Section: Introductionmentioning

confidence: 99%

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Periapical bone response to bacterial lipopolysaccharide is shifted upon cyclooxygenase blockage

Ribeiro-Santos¹,

Silva

Petean

et al. 2019

J. Appl. Oral Sci.

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Objectives: Infection, inflammation and bone resorption are closely related events in apical periodontitis development. Therefore, we sought to investigate the role of cyclooxygenase (COX) in osteoclastogenesis and bone metabolism signaling in periapical bone tissue after bacterial lipopolysaccharide (LPS) inoculation into root canals. Methodology: Seventy two C57BL/6 mice had the root canals of the first molars inoculated with a solution containing LPS from E. coli (1.0 mg/mL) and received selective (celecoxib) or non-selective (indomethacin) COX-2 inhibitor. After 7, 14, 21 and 28 days the animals were euthanized and the tissues removed for total RNA extraction. Evaluation of gene expression was performed by qRT-PCR. Statistical analysis was performed using analysis of variance (ANOVA) followed by post-tests (α=0.05). Results: LPS induced expression of mRNA for COX-2 (Ptgs2) and PGE 2 receptors ( Ptger1, Ptger3 and Ptger4 ), indicating that cyclooxygenase is involved in periapical response to LPS. A signaling that favours bone resorption was observed because Tnfsf11 (RANKL), Vegfa, Ctsk , Mmp9, Cd36 , Icam, Vcam1 , Nfkb1 and Sox9 were upregulated in response to LPS. Indomethacin and celecoxib differentially modulated expression of osteoclastogenic and other bone metabolism genes: celecoxib downregulated Igf1r, Ctsk , Mmp9, Cd36 , Icam1, Nfkb1 , Smad3, Sox9 , Csf3, Vcam1 and Itga3 whereas indomethacin inhibited Tgfbr1, Igf1r , Ctsk, Mmp9 , Sox9, Cd36 and Icam1 . Conclusions: We demonstrated that gene expression for COX-2 and PGE 2 receptors was upregulated after LPS inoculation into the root canals. Additionally, early administration of indomethacin and celecoxib (NSAIDs) inhibited osteoclastogenic signaling. The relevance of the cyclooxygenase pathway in apical periodontitis was shown by a wide modulation in the expression of genes involved in both bone catabolism and anabolism.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Periapical bone response to bacterial lipopolysaccharide is shifted upon cyclooxygenase blockage

Ribeiro-Santos¹,

Silva

Petean

et al. 2019

J. Appl. Oral Sci.

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“…TNF‐α is considered as a master regulator in the pathogenesis of periodontitis, participating in tissue destruction and osteoclastogenesis in periodontal diseases . Although few studies have made great progress in developing treatment strategies such as new classes of inhibitors that target TNF‐α or lipoxygenase to block the pathways responsible for periodontal tissue breakdown, the effect is far from ideal. Further study on the mechanisms of the molecular basis involved in periodontal diseases is essential to identify new targets and develop new techniques and strategies for the prevention and treatment of these diseases.…”

mentioning

confidence: 99%

Progranulin is highly expressed in patients with chronic periodontitis and protects against experimental periodontitis in rats

Xiao

Zuo

Chen

et al. 2018

Journal of Periodontology

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“…O LTB4 consegue exercer suas funções devido à sua ligação com os receptores acoplados à proteína G, denominados de receptores BLT1 e BLT2 (Lee et al, 2012), o que resulta em um aumento de cálcio intracelular e redução de adenosina 3',5'-monofosfato cíclico (cAMP), mediando assim a ativação de quinase, transcrição gênica, e o recrutamento de células (Paula-Silva et al, 2016). No entanto, enquanto que BLT1 é expresso principalmente em leucócitos, BLT2 é ubíquo.…”

Section: Lipoxigenase -Leucotrienos E Seu Papel Na Inflamação E Na Dounclassified

“…Esta sinalização de cálcio é capaz de ativar NFATc1 e iniciar a transcrição de genes relacionados com osteoclastos, como TRAP, catepsina K e integrina β3, facilitando o desenvolvimento de osteoclastos (Dixit et al, 2014). Além disso, o LTB4 inibe a proliferação das células precursoras de osteoblastos e a consequente formação óssea (Paula-Silva et al, 2016). Desta forma, na presença de inflamação, a liberação de LTB4 é aumentada a partir de monócitos/ macrófagos, o que leva a uma produção autócrina contínua dos mesmos, intensificando a osteoclastogênese (reabsorção óssea) (Jozefowski et al, 2005).…”

Section: Lipoxigenase -Leucotrienos E Seu Papel Na Inflamação E Na Dounclassified

Avaliação do efeito do antagonismo do receptor de leucotrienos na modulação da periodontite experimental em ratos

Moro¹

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Dedico este trabalho, primeiramente, аos meus pais que, cоm muito carinho е apoio, nunca mediram esforços para qυе еυ chegasse аté esta etapa dе minha vida. Dedico também às minhas irmãs, avós e companheiro. E, por fim, não menos importante, aos meus orientadores Marinella, Marcelo e Gilson e a todas as amizades que construí no decorrer desta engrandecedora caminhada." AGRADECIMENTOS À Deus, pois sem Ele nada é possível. À minha família, meu pai Nestor e mãe Evelise, minhas irmãs Mariana e Marjorie, meu cunhado João e minha vó Lourdes, pelo incentivo e apoio dado durante esta trajetória, fazendo com que o caminho percorrido tenha sido menos árduo. Ao meu namorado Gustavo Trevizoli, pelo apoio e incentivo em cada passo dado, além de toda a paciência por ele concedida em diferentes momentos. À minha orientadora Profa. Dra. Marinella Holzhausen Caldeira, a qual tão bem me acolheu e sempre acreditou no meu trabalho, me dando força para crescer e ser cada vez melhor. Ao meu co-orientador Prof. Dr. Marcelo Nicolás Muscará, o qual disponibilizou seu laboratório para toda execução do trabalho, além da transmissão de todo o conhecimento e experiência. À querida Simone Aparecida Teixeira, que esteve do meu lado em todos os momentos na execução dos experimentos, e acabou se tornando uma grande amiga. Ao Prof. Dr. Luis Carlos Spolidorio, o qual sempre se mostrou muito disposto a ajudar, sendo o responsável por toda a parte histológica do trabalho. Ao Prof. Dr. Gilson Cesar Nobre Franco, o qual me ajudou no desenvolvimento inicial do projeto e, mesmo de longe, esteve todo o momento me dando suporte e incentivo. À minha colega de laboratório Flavia Neto de Jesus, que me ensinou com todo carinho e paciência o modelo a ser desenvolvido. Às alunas de Iniciação Científica Marilia Dantas e Maria Mariante que fizeram um excelente trabalho, participando ativamente do desenvolvimento das metodologias. À dedicada Karla Feitosa, a qual nunca hesitou ajudar nos momentos em que necessitei. A toda equipe do Laboratório de Farmacologia Bioquímica dos radicais livres, inflamação e dor do ICB-USP,

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Dual Role of 5-Lipoxygenase in Osteoclastogenesis in Bacterial-induced Apical Periodontitis

Cited by 30 publications

References 39 publications

Periapical bone response to bacterial lipopolysaccharide is shifted upon cyclooxygenase blockage

Periapical bone response to bacterial lipopolysaccharide is shifted upon cyclooxygenase blockage

Progranulin is highly expressed in patients with chronic periodontitis and protects against experimental periodontitis in rats

Avaliação do efeito do antagonismo do receptor de leucotrienos na modulação da periodontite experimental em ratos

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